Marinus Pharmaceuticals Initiates Clinical Trial with Ganaxolone in PCDH19 Female Pediatric Epilepsy

Print 03 February 2015

RADNOR, Pa., Feb. 3, 2015 (GLOBE NEWSWIRE) -- Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS), a biopharmaceutical company dedicated to the development of innovative neuropsychiatric therapeutics, announced that it has initiated a Phase 2 clinical trial with ganaxolone, a synthetic analog of the endogenous neurosteroid allopregnanolone, in female children with epilepsy caused by a mutation of the protocadherin 19 gene (PCDH19). PCDH19 female pediatric epilepsy is a rare disease that is estimated to affect approximately 15,000-30,000 females in the U.S. and is characterized by onset of cluster seizures before age 5, cognitive and sensory impairment of varying degrees, and behavioral disturbances. There are currently no approved therapies for PCDH19 female pediatric epilepsy. The multicenter, open-label clinical trial is designed to evaluate the safety and efficacy of ganaxolone as adjunctive therapy for uncontrolled seizures in PCDH19 female pediatric epilepsy.  

"We are excited to advance the development of ganaxolone into this rare disease that affects the female pediatric population," commented Christopher M. Cashman, Chief Executive Officer of Marinus Pharmaceuticals. "This is an important step in our clinical development strategy to advance ganaxolone for the large epilepsy market while in parallel pursuing unmet medical needs in pediatric orphan indications, including PCDH19 female pediatric epilepsy."

This Phase 2 study is designed to enroll approximately 10 female pediatric patients between the ages of 2 and 10 years old, with a confirmed PCDH19 genetic mutation. After establishing baseline seizure frequency, patients will be treated with ganaxolone administered as either oral liquid suspension or capsules for up to 26 weeks. The primary endpoint of the study is percent change in seizure frequency per 28 days relative to baseline. Data from the study is anticipated later this year. 

Dr. Gail Farfel, Chief Clinical and Regulatory Officer of Marinus Pharmaceuticals, stated, "Scientific researchers have linked the PCDH19 mutation to low levels of allopregnanolone, a naturally occurring neurosteroid. We believe that the novel mechanism of ganaxolone, our synthetic analog of allopregnanolone, coupled with data from earlier trials conducted in pediatric patients with intractable seizures, provides sound rationale to develop ganaxolone for treatment of PCDH19 female pediatric epilepsy."

Ganaxolone has been previously evaluated in multiple studies of pediatric seizure disorders in children aged 4 months through 15 years. Across five studies, approximately two thirds of subjects experienced improvements in seizures and one third of subjects experienced improvements of 50% or greater from baseline seizure frequency. Most of the adverse events reported in the clinical development program were mild or moderate in severity, dose-related, resolved upon treatment discontinuation, and expected based on ganaxolone pharmacology. The most common adverse events across all clinical trials are dizziness, fatigue and somnolence. The adverse event profile of ganaxolone in pediatric studies is similar to that seen in adults, without evidence of unique, clinically meaningful adverse events specific to the pediatric population.

Marinus has established collaborative relationships with the PCDH19 Alliance and The Cute Syndrome Foundation, two patient advocacy groups focused on finding a cure for PCDH19 female pediatric epilepsy. For more information about the disease and the efforts of these groups, please visit their websites.

About PCDH19 Female Pediatric Epilepsy

PCDH19 female pediatric epilepsy is a serious and rare epileptic syndrome that affects approximately 15,000-30,000 females in the United States. The condition, which is caused by an inherited mutation of the protocadherin 19 (PCDH19) gene, located on the X chromosome, is characterized by early-onset cluster seizures, cognitive and sensory impairment of varying degrees, and behavioral disturbances. The PCDH19 gene encodes a protein, protocadherin 19, which is part of a family of molecules supporting the communication between cells in the central nervous system. In case of mutation, protocadherin 19 may be malformed, reduced in its functions or not produced at all. The abnormal expression of protocadherin 19 is associated with occurrence of seizures beginning in the early years of life, mostly focal clustered seizures that last from one day to weeks. Often, but not always, the syndrome is also associated with a cognitive impairment of varying nature, and behavioral or social disorders with autistic traits. Currently, there are no approved therapies for PCDH19 female pediatric epilepsy.

About Ganaxolone

Ganaxolone is a small molecule that is a synthetic analog of allopregnanolone, an endogenous neurosteroid produced in the central nervous system that modulates the brain neurotransmitter GABA. Ganaxolone was designed to have the same GABA modulation effects as allopregnanolone without steroidal effects. Ganaxolone and allopregnanolone differ from other GABA_A agents by interacting with unique binding sites on the GABAAreceptor that are located both within (synaptic) and outside (extrasynaptic) the GABA synapse. Ganaxolone's activation of the extrasynaptic receptor is a unique mechanism that provides stabilizing effects that we believe differentiates it from other drugs that increase GABA signaling. Preclinical studies provide evidence that the GABA modulatory activity of ganaxolone is responsible for its anticonvulsive activity in epileptic seizures and its antianxiety effects in FXS and other neuropsychiatric disorders.

About Marinus Pharmaceuticals

Marinus Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development of innovative neuropsychiatric therapeutics. The Company's clinical stage drug candidate, ganaxolone, is a novel synthetic analog of the endogenous neurosteroid, allopregnanolone. Ganaxolone is known for its anticonvulsive and antianxiety effects, and was designed to avoid hormonal side-effects associated with endogenous neurosteroids. Ganaxolone is presently being studied in a multinational, randomized, placebo-controlled, Phase 3 clinical trial in adult subjects for adjunctive treatment of partial-onset seizures. The Company has a Phase 2 proof-of-concept clinical study on-going with ganaxolone for the treatment of PCDH19 female pediatric epilepsy and a Phase 2 proof-of-concept investigator sponsored clinical trial evaluating ganaxolone as a treatment for behaviors in Fragile X Syndrome. Both PCDH19 female pediatric epilepsy and Fragile X Syndrome are potential orphan disorders that have been related to mutations affecting neurosteroid signaling at extrasynaptic GABA_A receptors. For additional information, please visit the Company's website at www.marinuspharma.com.

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding Marinus, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.  Words such as "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements.  Examples of forward looking statements contained in this press release include, among others, statements regarding our expectations regarding our development plans for our product candidate, including, potential for orphan designation, optimizing a product's formulation and the clinical trial testing schedule. Forward-looking statements in this release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements.  Such risks and uncertainties include, among others, the uncertainties inherent in the conduct of future clinical trials, the timing of the clinical trials, enrollment in clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals, and other matters, including the development of formulations of ganaxolone, that could affect the availability or commercial potential of our drug candidates.  Marinus undertakes no obligation to update or revise any forward-looking statements.  For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see filings Marinus has made with the Securities and Exchange Commission.          

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